Table 2.
Drug-drug interactions among direct-acting antivirals and calcineurin inhibitors
| Cyclosporine (CSA) | Tacrolimus (TAC) | Sirolimus (SRL) | Everolimus (EVR) | |
| Sofosbuvir (SOF) | 4.5-fold ↑ in SOF AUC No dose adjustment necessary | 13% ↑ in SOF AUC No dose adjustment necessary | Not studied, no interaction expected No dose adjustment necessary | Not studied, no interaction expected No dose adjustment necessary |
| Ledipasvir | Not studied, no interaction expected | Not studied, no interaction expected | Not studied, no interaction expected | Not studied, may increase EVR concentrations due to mild inhibition of P-gp by ledipasvir |
| Paritaprevir / ritonavir / ombitasvir + dasabuvir (PrOD) | 5.8-fold ↑ in CSA AUC Modeling suggests using 1/5 of CSA dose during PrOD treatment Frequent monitoring necessary | 57-fold ↑ in TAC AUC Modeling suggests TAC 0.5 mg every 7 days during PrOD treatment | 38-fold ↑ in SRL AUC Do NOT co-administer | 27.1-fold ↑ in EVR AUC Do NOT co-administer |
| Elbasvir / grazoprevir (EBR/GZR) | 15-fold ↑ in GZR AUC and 2-fold ↑ in EBR AUC Do NOT co-administer | 43% ↑ in TAC AUC No a priori dose adjustment necessary | Not studied, may increase SRL concentrations due to mild inhibition of P-gp by elbasvir | Not studied, may increase EVR concentrations due to mild inhibition of P-gp by elbasvir |
| Velpatasvir | No interaction observed; no a priori dose adjustment necessary | No data; no a priori dose adjustment necessary | No data; no a priori dose adjustment necessary | Not studied, may increase EVR concentrations due to mild inhibition of P-gp by velpatasvir |
| Glecaprevir / pibrentasvir (GLE/PIB) | 5-fold ↑ in GLE AUC with higher doses (400 mg) of CSA Not recommended in patients requiring stable CSA doses > 100 mg/day | 1.45-fold ↑ in TAC AUC No a priori dose adjustment, monitor TAC levels and titrate TAC dose as needed | Not studied, may increase SRL concentrations due to mild inhibition of P-gp by pibrentasvir | Not studied, may increase EVR concentrations due to mild inhibition of P-gp by pibrentasvir |
| Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) | 9.4-fold ↑ in VOX AUC Do NOT co-administer | No data; no a priori dose adjustment | Not studied, may increase SRL concentrations due to mild inhibition of P-gp by velpatasvir and voxilaprevir | Not studied, may increase EVR concentrations due to mild inhibition of P-gp by velpatasvir and voxilaprevir |
Adapted from www.hcvguidelines.org and www.hep-druginteractions.org. CsA: Cyclosporine; TAC: Tacrolimus; SRL: Sirolimus; EVR: Everolimus; SOF: Sofosbuvir; AUC: Area under the curve; PrOD: Paritaprevir/ritonavir, ombitasvir, and dasabuvir; ELB/GRZ: Elbasvir/grazoprevir; P-gp: P-glycoprotein; VOX: Voxilaprevir; VEL: Velpatasvir.